An early CT-diagnosis-based treatment strategy for invasive fungal infection in allogeneic transplant recipients using caspofungin first line: an effective strategy with low mortality.

Empirical antifungal therapy is frequently used in allogeneic transplant patients who have persistent febrile neutropenia and can be associated with high cost, toxicity and breakthrough infections. There are limited reports of strategies for early diagnosis of invasive fungal infection (IFI) and, to our knowledge, no reports of treatment strategies based only on high-resolution computerized tomography (HRCT) scans. We used an early treatment strategy for IFI in 99 consecutive patients undergoing allogeneic transplantation. Patients received caspofungin if they had antibiotic-resistant neutropenic fever for more than 72 h and a positive HRCT scan. Fifty-three of 99 patients (54%) had antibiotic-resistant neutropenic fever at 72 h and would have received parenteral antifungal treatment if an empirical approach had been used. The HRCT-based strategy reduced the use of parenteral antifungal agents to 17/99 patients (17%), a 68% reduction. No subsequent diagnoses of IFI occurred within 100 days in patients with a negative HRCT. Only one patient died from IFI within 100 days. These data suggest that this non-empirical strategy may be feasible and that caspofungin may be effective in this setting. A randomized controlled trial is warranted to further assess these results.

A prospective study of admissions for febrile neutropenia in secondary paediatric units in South East England.

BACKGROUND: The Paediatric Oncology Centres (POCs) treating childhood cancer in South East England produce unified supportive care guidelines for use in the secondary pediatric (shared care) units. This study evaluated the adherence to current guidelines for febrile neutropenia (FN) and documented outcome in terms of bacterial isolates, antibiotic resistance patterns, length of hospital stay, and mortality. PROCEDURE: Prospective study of pediatric FN admissions between July 2001 and December 2002. RESULTS: Data were received on 433 eligible FN episodes in 212 patients. The recommended empirical antibiotics (piptazobactam + gentamicin) were used in 354 (82%) admissions. Blood cultures were positive in 129 episodes (30%). Gram-positive organisms predominated (120/149 organisms isolated) and the majority were coagulase-negative Staphylococci (95/120). There were 27 Gram-negative isolates and 1 fungal isolate. No Gram-negative isolate was resistant to both first-line antibiotics. Only one death was recorded in the study group. The median length of hospital stay was 5 days. CONCLUSIONS: We obtained data on a large number of shared care episodes of FN. The antibiotic guidelines were followed in most episodes. Bacteremia was common, but little resistance to first-line antibiotics was documented among Gram-negative isolates, confirming the safety of the strategy in our population.

Parainfluenza type 3 infection post stem cell transplant: high prevalence but low mortality.

Parainfluenza type 3 (PIV 3) is a well-recognized cause of respiratory illness after stem cell transplantation (SCT), with an estimated incidence of 2-7% and a high mortality rate associated with lower respiratory tract infection (LRTI). A 12-month retrospective study was undertaken in which 23 positive cases of PIV 3 occurred in SCT recipients. The frequency of infection was 36.1% in matched unrelated donor SCT recipients, 23.8% in sibling allogeneic SCT recipients and 2.3% in autologous transplant recipients. Seventeen cases were outpatient or community acquired despite standard infection control measures. Eleven patients only developed upper respiratory tract symptoms. LRTI symptoms developed in 12 patients, of whom eight had a new infiltrate on chest X-ray. Overall mortality at 30 days from PIV 3 diagnosis was 4% (one patient). Four patients died within 100 days of PIV 3 diagnosis, but PIV 3 was not believed to be the primary cause of death in any of these patients. Early ribavirin was used in eight patients and only one patient who received ribavirin died. These results suggest a higher prevalence of PIV 3 but a lower mortality than documented previously, particularly in allogeneic transplant recipients. The authors propose that the high prevalence reflects the unit's policy of active surveillance for respiratory viruses and the difficulty in preventing transmission of PIV 3, especially in the outpatient setting during an outbreak period. Ribavirin treatment may improve outcome in patients with LRTI but is not required in all patients with PIV 3.

Role of itraconazole in haematology/oncology.

The antifungal agents most frequently used in prophylaxis and treatment are amphotericin B (and its new lipid forms) and azoles such as fluconazole, itraconazole, and more recently voriconazole. This review assesses the role of itraconazole in paediatric haematology/oncology practice. Its broader spectrum of activity and availability in oral and intravenous forms allow a flexible approach in the management of fungal infections.

Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants.

Incidences of and risk factors for Streptococcus pneumoniae sepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P =.03) and chronic GVHD (10-year probability, 14% vs 4%; P =.002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127; P =.07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16; P =.04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk. (Blood. 2000;95:3683-3686)

Systemic candidiasis with candida vasculitis due to Candida kruzei in a patient with acute myeloid leukaemia.

Candida kruzei-related systemic infections are increasing in frequency, particularly in patients receiving prophylaxis with antifungal triazoles. A Caucasian male with newly diagnosed acute myeloid leukaemia (AML M1) developed severe and persistent fever associated with a micropustular eruption scattered over the trunk and limbs during induction chemotherapy. Blood cultures grew Candida kruzei, and biopsies of the skin lesions revealed a candida vasculitis. He responded to high doses of liposomal amphotericin B and was discharged well from hospital.

Successful treatment of Aspergillus fungaemia in two children with acute lymphoblastic leukaemia.

Aspergillus species can cause life-threatening infection in immunocompromised children. Pulmonary infections are the most common, and are usually acquired through inhalations of aspergillus spores in unfiltered air. Some patients acquire invasive aspergillus infection from endogenous spread of colonized para-nasal sinuses.